{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:29:19Z","timestamp":1790094559008,"version":"4.0.1"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SKLID Development Grant","award":["2021SKLID504"],"award-info":[{"award-number":["2021SKLID504"]}]},{"name":"SKLID Development Grant","award":["2019SKLID401"],"award-info":[{"award-number":["2019SKLID401"]}]},{"name":"SKLID Development Grant","award":["2019SKLID603"],"award-info":[{"award-number":["2019SKLID603"]}]},{"name":"SKLID Development Grant","award":["2016SKLID603"],"award-info":[{"award-number":["2016SKLID603"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFC2306000"],"award-info":[{"award-number":["2023YFC2306000"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFC0863000"],"award-info":[{"award-number":["2021YFC0863000"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFC1200305"],"award-info":[{"award-number":["2018YFC1200305"]}]},{"name":"Tengfei initiative","award":["2024NITFID507"],"award-info":[{"award-number":["2024NITFID507"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Creutzfeldt\u2013Jakob disease (CJD) is a rare but devastating neurodegenerative disorder characterized by the pathological misfolding of the cellular prion protein (PrPC) into the pathogenic isoform-scrapie prion protein (PrPSc), ultimately leading to fatal outcomes. Cerebrospinal fluid (CSF) biomarkers play a pivotal role in early diagnosis, longitudinal monitoring, and prognostic assessment, thereby enhancing the clinical management of this challenging disease. This review summarizes the established CSF biomarkers, 14-3-3 protein, tau protein (total tau), phosphorylated tau isoforms, \u03b1-synuclein, neurofilament light chain (Nfl), S100B, neuron-specific enolase (NSE), and phosphorylated neurofilament heavy chain (pNFH), highlighting typical sensitivity ranges (14-3-3 ~70\u201385%; RT-QuIC &gt; 90%) and subtype-dependent performance variation. We further dissect limitations related to assay variability, inter-laboratory cut-off inconsistencies, and reduced specificity in non-prion dementias. Looking ahead, we discuss emerging multi-omics discovery, integration of CSF with blood-based biomarkers and imaging signatures, and AI-enabled diagnostic modeling. We propose a three-tier biomarker framework combining Real-Time Quaking-Induced Conversion (RT-QuIC) as a confirmatory assay, tau\/NfL\/pNFH as injury-severity indicators, and multi-omics-derived signatures for early detection and prognosis stratification.<\/jats:p>","DOI":"10.3390\/ijms27010553","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T08:42:58Z","timestamp":1767688978000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cerebrospinal Fluid Biomarkers in Creutzfeldt\u2013Jakob Disease: Diagnostic Value, Limitations, and Future Multi-Omics Strategies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6770-6073","authenticated-orcid":false,"given":"Rui","family":"Xu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, Beijing Key Laboratory of Viral Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-9283","authenticated-orcid":false,"given":"Cao","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, Beijing Key Laboratory of Viral Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 100084, China"},{"name":"Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, Beijing Key Laboratory of Viral Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"},{"name":"China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Dong","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, Beijing Key Laboratory of Viral Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 100084, China"},{"name":"Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"},{"name":"China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Shanghai Institute of Infectious Disease and Biosafety, Shanghai 200003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Senesi, M., Lewis, V., Varghese, S., Stehmann, C., McGlade, A., Doecke, J.D., Ellett, L., Sarros, S., Fowler, C.J., and Masters, C.L. 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